Effects of AMP579 and adenosine on L‐type Ca2+ current in isolated rat ventricular myocytes

Aim: To compare the effects of AMP579 and adenosine on L-type Ca 2+ current ( I Ca-L ) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on I Ca-L . Methods: I Ca-L was recorded by patch-clamp technique in whole-cell configuration. Results: Adenosine (10 nmol/L to 50 umol/L) showed no effect on basal I Ca-L , but it inhibited the I Ca-L induced by isoproterenol 10 nmol/L in a concentration-dependent manner with the IC 50 of 13.06 umol/L. Similar to adenosine, AMP579 also showed an inhibitory effect on the I Ca-L induced by isoproterenol. AMP579 and adenosine (both in 10 umol/L) suppressed isoproterenol-induced I Ca-L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal I Ca-L in a concentration-dependent manner with IC 50 (1.17 mumol/L). PD116948 (30 mumol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal I Ca-L . However, GF109203X (0.4 mumol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal I Ca-L . So the inhibitory effect of AMP579 on basal ICa-L was induced through activating PKC, but not linked to adenosine A 1 receptor. Conclusion: AMP579 shows a stronger inhibitory effect than adenosine on the I Ca-L induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal ICa-L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal I Ca-L at downstream-mechanism.